Biodistribution and toxicity assessment of europium-doped Gd₂O₃ nanotubes in mice after intraperitoneal injection

In order to evaluate the biodistribution and toxicity of europium-doped Gd₂O₃ nanotubes, we synthesized Gd₂O₃:Eu³⁺ nanotubes via a simple wet-chemical route at ambient pressure. The as-obtained Gd₂O₃:Eu³⁺ sample is composed of uniform and well-dispersed nanotubes. The diameters and lengths of the nanotubes are about 50 and 300 nm, respectively. All mice of the experimental groups were administered by intraperitoneal injection everyday over a period of 60 days at doses ranging from 1.25 to 125 mg/kg. Haematological and biochemical parameters and histopathology were examined, and the biodistribution of Gd element in different organs was analyzed. The results indicate that the spleen shows significant higher coefficient than the control, and other organs have no obvious difference from the control in the middle-dose and high-dose groups. There was no significant difference in the blood-elements between the control group and the experimental groups, and no significant change of all parameters can be observed in both low-dose and middle-dose groups. However, in the high-dose group, the ALT, AST, the ratio of AST/ALT, UA, LDH, and HBDH levels was increased significantly in comparison with the control group. The pathology results show that the ischemia of myocardial cell, hemorrhage of lung tissue, hepatocyte necrosis, congestion of renal interstitium, mesangial cell proliferation, and congestion of spleen sinus were induced by high-dose Gd₂O₃:Eu³⁺ nanotubes. Biodistribution experiment exhibits that Gd mainly accumulates in spleen, lung, and liver. Therefore, it can be concluded that high-dose Gd₂O₃:Eu³⁺ nanotubes were toxic, but low-dose and middle-dose groups did not show significant toxicity. The results provide novel toxicology data of Gd₂O₃:Eu³⁺ nanotubes and may be helpful for more rational applications of Gd-based compounds in the future.